Dexmedetomidine Attenuates Neuropathic Pain by Inhibiting P2X7R Expression and ERK Phosphorylation in Rats

α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state. Behavioral hypersensitivity to mechanical and thermal stimuli was determined by von Frey filament and Hargreaves' tests, and the spinal P2X7R expression level and ERK phosphorylation were analyzed using western blot analysis and immunohistochemistry. In parallel with the development of mechanical and thermal hyperalgesia, a significant increase in P2X7R expression was noted in the ipsilateral spinal cord on day 7 after CCI. Intrathecal administration of dexmedetomidine (2.5 µg) for 3 days not only attenuated neuropathic pain but also inhibited the CCI-induced P2X7R upregulation and ERK phosphorylation. Intrathecal dexmedetomidine administration did not produce obvious effects on locomotor function. The present study demonstrated that dexmedetomidine attenuates the neuropathic pain induced by CCI of the sciatic nerve in rats by inhibiting spinal P2X7R expression and ERK phosphorylation, indicating the potential therapeutic implications of dexmedetomidine administration for the treatment of neuropathic pain.

Epidural fentanyl decreases the minimum local analgesic concentration of epidural lidocaine / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidural lidocaine can be used when regional anesthesia needs to be established quickly, but the effect of co-administering epidural fentanyl on the minimum local analgesic concentration (MLAC) of lidocaine is not known. We compared the MLAC of epidural lidocaine in combination with different doses of fentanyl for epidural anesthesia in adults.</p><p><b>METHODS</b>One hundred and twenty patients requiring epidural analgesia were randomly allocated to receive 20 ml of one of four solutions: lidocaine, or lidocaine plus fentanyl 1 µg/ml, 2 µg/ml, or 3 µg/ml. The first patient in each group was administered 1% lidocaine weight by volume; subsequent patients received a concentration determined by the response of the previous patient to a higher or lower concentration according to up and down sequential allocation in 0.1% increments. Efficacy was assessed using a visual analog pain scale, and accepted if this was = 10 mm on a 100 mm scale within 30 minutes. The extent of motor block and of nausea and vomiting were recorded at 30 minutes after administration of the epidural solution and two hours after surgery, respectively.</p><p><b>RESULTS</b>The MLAC of lidocaine in those receiving lidocaine alone was 0.785% (95%CI 0.738 - 0.864). A significant dose-dependent reduction was observed with the addition of fentanyl: the MLAC of lidocaine with fentanyl at 2 µg/ml was 0.596% (95%CI 0.537 - 0.660) and 0.387% with fentanyl at 3 µg/ml (95%CI 0.329 - 0.446, P < 0.001).</p><p><b>CONCLUSION</b>Epidural fentanyl significantly reduces the dose of lidocaine required for effective epidural analgesia in adults without causing adverse side effects.</p>